Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of combination chemotherapy in the treatment of advanced non-small-cell lung cancer is controversial. At best, a small survival benefit can be achieved. Therefore, other treatment modalities are needed. On the basis of the promising treatment results with interleukin-2 (IL-2) -containing immunotherapy in renal cell cancer and melanoma, we performed a phase I-II study with IL-2 and interferon alpha (IFN-alpha). Eligible patients were treated with IL-2 18 x 10(6) IU/m2/day by continuous intravenous infusion (c.i.v.) for 3 days. On the same days, 5 x 10(6) U/m2/day IFN-alpha was given intramuscularly. After a rest period of 4 days, patients at the first dose level received IL-2 2.4 x 10(6) IU/m2/day c.i.v. for a period of 28 days, followed by 14 days' rest, 14 days' treatment, 7 days' rest, and a final treatment for 14 days. Patients at the second dose level were treated according to the same schedule, in which the dose of IL-2 was increased to 3.6 x 10(6) IU/m2/day. During low-dose IL-2 treatment, patients received IFN-alpha 5 x 10(6) U/m2/day on days 1 and 4 of each week. Eleven patients were admitted to the study, six at the first and five at the second dose level. Median age was 54 years; all patients had a performance status of 0 or 1. The most important adverse effects included anorexia, fatigue, nausea, and headache, which were not dose limiting. In the 11 patients treated, no responses were seen. Nine patients developed progressive disease during the first 5 weeks of treatment. We concluded that this regimen of IL-2 and IFN-alpha is ineffective.
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PMID:Interleukin-2 and interferon-alpha in the treatment of patients with advanced non-small-cell lung cancer. 132 67

Fifteen patients with metastatic renal cell carcinoma (RCC) were treated by administration of autologous lymphokine-activated killer (LAK) cells given together with systemic administration of interleukin-2 (IL-2). Pulmonary metastases alone were found in 10 cases, pulmonary and mediastinal nodal metastases in 3, and pulmonary and bone metastases in 2. LAK cells, generated by incubation in 700 units/ml of IL-2 for 3-4 days, were intravenously administered once a week. In addition, beginning on the day of the first LAK cell infusion, 3.5 x 10(5) units of IL-2 were intravenously infused once or twice a day with occasional supplementation of 3.5 x 10(5) units of IL-2 on each day of LAK cell infusion. The total number of LAK cells and total amount of IL-2 administered per patient in this study ranged from 0.8 x 10(10) to 6.9 x 10(10) cells and from 10.2 x 10(6) to 74.9 x 10(6) units, respectively. As toxic effects caused by the infusion of LAK cells, headache, shaking chills, fever and leukocytosis were found in all cases. Side effects possibly induced by IL-2 infusion were tolerable fever, fluid retention (body weight gain of 2-3 kg) and eosinophilia. Out of 15 patients, a partial response was observed in 4 patients who had pulmonary metastases alone. One of the 4 patients with a partial response was clinically free of disease after undergoing a thoracotomy for resection of residual lesions, but a brain metastasis was detected 10 months after the thoracotomy. The remaining 3 patients are being closely followed up at present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Lymphokine-activated killer (LAK) therapy for metastatic renal cell carcinoma]. 148 86

Nine patients with a recurrent malignant glioma were treated with repeated intracavitary or intracerebroventricular injections of human recombinant interleukin-2 (rIL-2) alone or in combination with systemic interferon-alpha (IFN-alpha). Five patients received only rIL-2 and four were treated with rIL-2 plus subcutaneous injections of IFN-alpha. Therapy was administered on a Monday, Wednesday, Friday schedule for up to 10 weeks, beginning with a dose of 10,000 IU rIL-2/injection. Doses were escalated every two weeks until some toxicity was apparent. The maximum amount of rIL-2 any one patient in this group received was 580,000 IU. Patients on combination immunotherapy were held at an rIL-2 dosage of 10,000 IU while IFN-alpha, which began at 3 million IU, was escalated every other week up to 18 million IU/dose. They were then held at that IFN-alpha dosage and rIL-2 was increased to 50,000 IU. The total amount of rIL-2 and IFN-alpha any one in this group received was 510,000 IU and 417 million IU, respectively. Repeated injections of 10,000 IU rIL-2 were well-tolerated by all nine patients and no change in their functional status was seen. At doses at 50,000 IU rIL-2, increased edema around the tumor cavity was observed by MRI/CT scand in 3/5 patients and clinical side-effects in the form of somnolence and headache along with some morbidity specifically associated with tumor location were also seen. Patients receiving rIL-2+ IFN-alpha showed progressive fatigue, muscle weakness, and occasionally nausea. Two of these patients showed increased peritumoral edema on MRI/CT scan.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of recurrent malignant glioma by repeated intracerebral injections of human recombinant interleukin-2 alone or in combination with systemic interferon-alpha. Results of a phase I clinical trial. 154 81

Colony-stimulating factors (CSFs) are hematopoietic growth hormones that stimulate the production, maturation, and function of white blood cells. The best studied are granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF), both of which can be produced by recombinant DNA technology. Clinical indications for these agents include bone marrow failure secondary to administration of chemotherapeutic drugs or radiation, bone marrow transplantation, and a variety of congenital or iatrogenic neutropenias. Toxicity in usual clinical doses is mild, and consists mainly of bone pain and constitutional symptoms such as fever, headache, and myalgias. Interleukin-2 (IL-2) is a lymphokine that stimulates that multiplication of several types of killer cells. These cells can recognize and destroy foreign substances, such as tumors, without destroying normal cells. Major applications of IL-2 include treatment of patients with renal cell carcinoma, in whom the overall objective response rate is 15-30 percent, and malignant melanoma with response rates of about 18 percent. Combination therapy with other biologics and conventional cytotoxic drugs may increase IL-2's efficacy against these tumors. Toxicity is generally severe, but reversible. Hemodynamic toxicity, consisting of hypotension, edema, weight gain, and decreased renal function, is most characteristic. Suggestions are given for pharmacologic management of these and other IL-2 toxicities.
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PMID:Clinical use of biologic response modifiers in cancer treatment: an overview. Part II. Colony-stimulating factors and interleukin-2. 171 21

Some cellular immune functions are impaired in cluster headache patients. Interleukin-2 (IL-2) is a polypeptide secreted by antigen or mitogen-actuated T lymphocytes that functions as a growth factor for T cells. To investigate cellular immune functions in patients with chronic headache, we measured the IL-2 concentration of sera in patients with migraine and in patients with tension-type headache. Thirteen subjects suffering from migraine without aura (5 males and 8 females, mean age: 32.8 years) and 46 subjects (20 males and 26 females, mean age: 39.7 years) with tension-type headache (TH) were selected for this study. Forty-three normal healthy volunteers composed the control group (15 males and 28 females, average age 41.6 years). The IL-2 levels of sera were determined using enzyme-linked immunosorbent assay (ELISA) techniques. The IL-2 levels of sera were 3.18 +/- 1.8 U/ml (mean +/- SD) in the healthy controls, 2.29 +/- 2.6 U/ml in the patients with migraine and 1.59 +/- 1.0 U/ml in the patients with TH. The serum level of IL-2 in the patients with migraine was significantly lower than in the controls. The serum level of IL-2 in the patients with TH was significantly lower than in the controls. The central nervous system (CNS) has been considered to be involved in the development of the immune phenomena. In the patients with TH or migraine, reduction in platelet 5-hydroxytryptamine (5-HT) levels and sympathetic hypofunction have been observed. These phenomena might reflect decrease in 5-HT levels in CNS in the patients with TH or migraine. The decreased serum IL-2 level, observed in this study, might reflect a reduction in 5-HT or catecholamine levels in CNS in the patients with migraine or TH.
Headache 1991 May
PMID:Decreased serum interleukin-2 level in patients with chronic headache. 186 Jul 89

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.
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PMID:Biologic effects of recombinant human interleukin-3 in vivo. 196 May 53

A 42-year-old man developed leptomeningeal carcinomatosis 6 years after treatment of a malignant melanoma. He was treated with two courses of recombinant interleukin-2, administered as a continuous intraventricular infusion (6 X 10E5 U/24 h) during 5 days. During the first day of the first course he also received 5 X 10E9 lymphokine-activated killer cells intraventricularly. This gave rise to a severe elevation of intracranial pressure, with headaches and meningismus. During the second course no LAK cells were administered. This course was tolerated much better. The neurological status did not change during the treatment. Recombinant interleukin-2 levels were maintained at about 300 U/mL during both courses.
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PMID:Treatment of leptomeningeal carcinomatosis with continuous intraventricular infusion of recombinant interleukin-2. 199 55

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated by systemic administration of autologous lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2). Pulmonary metastases alone were found in 9 cases, pulmonary and mediastinal nodal metastases in 3, and pulmonary and bone metastases in 2. LAK cells, generated by incubation in 2 units/ml of IL 2 for 3-4 days, were intravenously administered once or twice a week. In addition, beginning on the day of the first LAK cell infusion, 1000 units of IL 2 diluted in normal saline were intravenously infused once or twice a day with occasional supplementation of 1000 units of IL-2 on each day of LAK cell infusion. The total number of LAK cells and total amount of IL-2 administered per patient in this study ranged from 0.8 x 10(10) to 6.9 x 10(10) cells and from 3.3 x 10(4) to 21.4 x 10(4) units, respectively. As toxic effects caused by the infusion of LAK cells, headache, shaking chills, fever and leukocytosis were found in all 14 cases. Side effects possibly induced by IL-2 infusion were tolerable fever, fluid retention (body weight gain of 2-3 kg) and eosinophilia. No objective regression of mediastinal nodal or bone metastases was observed. In regard to lung metastases, however, partial and minor responses were observed in 3 and 2 cases, respectively. One of the 3 patients with a partial response was clinically free of disease after undergoing a thoracotomy for resection of residual lesions, but a brain metastasis was detected 10 months after the thoracotomy. The remaining 2 patients are being closely followed up at present. In 3 of 11 patients who showed a minor response, no change or progressive disease, brain metastases were observed during or after the immunotherapy. Furthermore, we examined the possibility of selection of suitable candidates for this therapy on the basis of the degree of in vitro LAK activity against autologous cultured tumor cells in 6 patients, but there was no significant correlation between in vitro autologous tumor cell lysis by LAK cells and the clinical response to immunotherapy. In conclusion, although a complete response could not be obtained, it can be said that this immunotherapy may be effective against RCC, in particular lung metastases, since a partial response was achieved in 3 of 14 patients. However, it should be taken into consideration that this immunotherapeutic approach may have a risk of increasing the frequency of brain metastases.
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PMID:[Usefulness and limitation of immunotherapy of metastatic renal cell carcinoma with autologous lymphokine-activated killer cells and interleukin 2]. 207 2

A case of long-term survival of a female patient with complicated diffuse metastatic leptomeningeal carcinomatosis (DMLC) secondary to lung cancer is reported. A 36-year-old woman, hospitalized with a chief complaint of headache and unproductive cough, was diagnosed as having primary lung adenocarcinoma (T4N1M1 oss) and was given systemic chemotherapy. Although progressive deterioration of her headache continued, repeated neurological examination, cerebrospinal fluid (CSF) examination, and cranial CT scans failed to show evidence of metastasis to the central nervous system, and the only finding suggesting CNS involvement was an elevated CEA level in CSF. Later in the course of her treatment, the patient suddenly lost her vision and subsequently consciousness due to acute increased intracranial pressure, and emergency ventricular drainage was performed for therapeutic and diagnostic purposes. Malignant cells were found in CSF obtained from a ventricular drainage and she was treated successfully by systemic and intrathecal chemotherapeutic agents. She was discharged after a ventriculoperitoneal shunt operation for hydrocephalus; a double-dome reservoir was used for continuous intrathecal administration of the anticancer drugs, and a shunt filter was located in the tube to prevent the dissemination of cancer cells. In addition to methotrexate and cytosine arabinoside, ACNU and interleukin-2 were administered intrathecally without serious adverse effects, but no apparent therapeutic effects were noted either. She survived over 2 years after DMLC was first diagnosed. At autopsy DMLC secondary to lung adenocarcinoma was confirmed, but no evidence of leukoencephalopathy due to aggressive intrathecal chemotherapy was found. Current therapy for patients with DMLC and its clinical problems are discussed in relation to our experience in this case.
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PMID:[A case of long-term survival of a patient with complicated diffuse metastatic leptomeningeal carcinomatosis secondary to lung adenocarcinoma]. 224 65

In a previous study we demonstrated that cluster headache (CH) patients present an increased Natural Cytotoxic response after incubation of their peripheral blood lymphocytes (PBL) with Interleukin-2 (IL-2). This phenomenon led to an investigation of the phenotypic expression of PBL before and after IL-2 incubation, and of the IL-2 lymphocyte receptor. IL-2 receptor is expressed on T-lymphocytes activated with an high-affinity binding site. The analysis of the function of human IL-2 receptor was facilitated by the production of a specific monoclonal antibody (MAb). This MAb identifies the IL-2 receptors by blocking the binding of radiolabelled IL-2 to T-cells. In addition, we studied the expression of Leu-4, specific for T-cells; of Leu-11b, specific for FC receptor on NK cells; and the Transferrin Receptor, specific for lymphoblasts and monocytes. Twenty-three episodic CH patients were selected for this study. Ten sex and age-matched healthy volunteers were used as the control group. We evaluated the PBL phenotypic expression of cells subsets before incubation with IL-2 (1,000 I.U./ml) and after 72 hours. The following Becton Dickinson MAbs have been used: anti-Leu-4 (CD3), anti-IL-2 receptors (CD25), anti-Transferrin receptor (TFR) and anti-Leu-11b (CD16). Indirect fluorescence with a Becton Dickinson FACS-420 flow cytometer was used to analyze the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Headache 1990 Mar
PMID:Defective expression of IL-2 receptors on peripheral blood lymphocytes from patients with cluster headache. 233 78


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